Journal article

NEXMIF encephalopathy: an X-linked disorder with male and female phenotypic patterns

Hannah Stamberger, Trine B Hammer, Elena Gardella, Danique RM Vlaskamp, Birgitte Bertelsen, Simone Mandelstam, Iris de Lange, Jing Zhang, Candace T Myers, Christina Fenger, Zaid Afawi, Edith P Almanza Fuerte, Danielle M Andrade, Yunus Balcik, Bruria Ben Zeev, Mark F Bennett, Samuel F Berkovic, Bertrand Isidor, Arjan Bouman, Eva Brilstra Show all

GENETICS IN MEDICINE | SPRINGERNATURE | Published : 2020

Abstract

PURPOSE: Pathogenic variants in the X-linked gene NEXMIF (previously KIAA2022) are associated with intellectual disability (ID), autism spectrum disorder, and epilepsy. We aimed to delineate the female and male phenotypic spectrum of NEXMIF encephalopathy. METHODS: Through an international collaboration, we analyzed the phenotypes and genotypes of 87 patients with NEXMIF encephalopathy. RESULTS: Sixty-three females and 24 males (46 new patients) with NEXMIF encephalopathy were studied, with 30 novel variants. Phenotypic features included developmental delay/ID in 86/87 (99%), seizures in 71/86 (83%) and multiple comorbidities. Generalized seizures predominated including myoclonic seizures an..

View full abstract

Grants

Awarded by Fund for Scientific Research Flanders


Awarded by National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)


Awarded by Key Research Project of the Ministry of Science and Technology of China


Funding Acknowledgements

We thank the patients and their families for participating in our research. We further want to acknowledge the Epi25 Consortium for providing a platform for exome sequencing for epilepsy patients that led to a diagnosis for some of the patients included in this study. H.S. was PhD fellow of the Fund for Scientific Research Flanders (1125416N). H.C.M. received support from the National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) (R01NS069605). D.M.A. received funding from EpLink, of the Ontario Brain Institute for array comparative genomic hybridization (aCGH) analysis. This study was supported by the Key Research Project of the Ministry of Science and Technology of China (2016YFC0904400 and 2016YFC0904401; through J.Z. and Y.A.Z.), Cure Kids New Zealand (through L.G.S.) and the Victorian Government's Operational Infrastructure Support Program and the Australian Government National Health and Medical Research Council (NHMRC) Independent Medical Research Institutes Infrastructure Support Scheme (IRIISS) (through M.B.). The work was generated within ITHACA (Intellectual disability, TeleHealth, And Congenital Anomalies), European Reference Network on Rare Congenital Malformations, and Rare Intellectual Disability.